Interstitial cystitis/painful bladder syndrome (IC/PBS) is a common chronic bladder syndrome characterized by bladder pain and discomfort (urgency) and increased frequency of urination. It is associated with significant decrements in health-related quality of life (HRQOL), productivity and increased healthcare costs. There is growing evidence that IC/PBS shares several features with other chronic functional pain disorders like irritable bowel syndrome (IBS) and fibromyalgia, including a history of adverse early life events, a history psychological or physical stressors preceding symptom onset or exacerbation, and the presence of anxiety and/or depression and poor illness coping. These findings suggest a model of IC/PBS development that includes vulnerability factors of childhood trauma interacting with life stress, familial modeling, and poor coping. These factors most likely interact with genetic vulnerabilities for both central and peripheral risk (including affective dysregulation) as well as bladder disease history. The proposed project follows the overall themes for the UCLA MAPP Center using a targeted epidemiology approach to study moderators and mediators of IC/PBS symptoms and symptom impact over a 1-year period in a diverse group of male and female patients. In Aim 1 we will examine IC/PBS patients bi-monthly for 1 year to characterize patients in terms of severity, frequency, and variation in cardinal symptoms, HRQOL, productivity, and healthcare utilization. We will examine concurrent mediators of symptom presentation including stress, coping and symptom-specific anxiety. In Aim 2, we will examine early life vulnerability factors including genetic traits, early life trauma, and familial modeling as moderator variables in the model to test the important hypotheses that these factors are related to adult symptom presentation including comorbidities with affective and other functional pain disorders and response to the mediating variables. In Aim 3, we will apply the same modeling to a sample of IBS patients to test the hypothesis that similar mediators and moderators operate in other functional pain disorders including genetic and early life vulnerabilities and ongoing stressors. Other important outcomes from this project will be the development of a IC/PBS targeted measure of symptom-specific anxiety, data on treatment response as related to the model predictors and new data on symptom variation over an extended period of time. If verified the proposed model of IC/PBS symptom development has important implications for a better understanding of underlying mechanisms as well as for more effective treatment strategies.